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Review
. 2025 Jan 13;13(2):141.
doi: 10.3390/healthcare13020141.

The Safety Profile of Inclisiran in Patients with Dyslipidemia: A Systematic Review and Meta-Analysis

Maisha Maliha  1   2 , Vikyath Satish  1   2 , Sriram Sunil Kumar  1   2 , Kuan Yu Chi  1   2 , Nishat Shama  3 , Amrin Kharawala  1   2 , Gustavo Duarte  4 , Weijia Li  5 , Sutopu Purkayastha  6 , Shaunak Mangeshkar  1   2 , Pawel Borkowski  1   2 , Eleonora Gashi  1   2 , Supreeti Behuria  6
Affiliations
Review

The Safety Profile of Inclisiran in Patients with Dyslipidemia: A Systematic Review and Meta-Analysis

Maisha Maliha et al. Healthcare (Basel). .

Abstract

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. It has demonstrated a significant reduction in LDL cholesterol levels compared to a placebo. We aim to comprehensively evaluate the safety of using Inclisiran in patients with dyslipidemia and ASCVD or an ASCVD risk equivalent.

Methods: Four electronic databases, namely, Pubmed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, were searched from inception to June 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of Inclisiran and the control group. The outcomes investigated were all-cause mortality, major adverse cardiovascular events (MACEs), injection-site adverse events, new-onset or worsening type 2 diabetes mellitus (T2DM), and nasopharyngitis. The effect estimates of outcomes were assessed using the risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method. Subgroup analysis was performed based on different dosing regimens.

Results: The study included 7 RCTs, enrolling 4790 patients (age 63.8 ± 9.7 years, 33.2% females) who received Inclisiran. Compared to the control group, Inclisiran use did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I2 = 0%), MACEs (RR, 0.98; 95% CI, 0.82 to 1.17; I2 = 0%), nasopharyngitis (RR, 1.10; 95% CI, 0.83 to 1.45; I2 = 0%), and T2DM (RR, 1.02; 95% CI, 0.85 to 1.21; I2 = 0%). However, Inclisiran use demonstrated a significant increase in injection-site adverse events (RR, 6.50; 95% CI, 3.20 to 13.20; I2 = 29%).

Conclusions: Inclisiran use significantly increased injection-site reactions, with no increase in mortality, T2DM, or nasopharyngitis. It demonstrates a generally favorable safety profile, making it a promising option for lipid management in individuals at high cardiovascular risk, such as those with ASCVD or equivalent conditions. While it effectively improves dyslipidemia, decision-makers should be aware of an increased incidence of injection-site reactions, which, though typically mild, warrant consideration in clinical practice. Further trials are required to assess the safety of Inclisiran, particularly the association of the severity of injection-site adverse events over longer treatment durations.

Keywords: LDL; inclisiran; lipid; safety.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
A PRISMA flow diagram. Summary: The PRISMA flow diagram summarizes the study selection process, where 218 studies were screened, 6 were included in the final qualitative and quantitative synthesis, and the rest were excluded due to duplication, irrelevant interventions, or a lack of eligibility criteria.
Figure 2
Figure 2
Funnel plot analysis.
Figure 2
Figure 2
Funnel plot analysis.
Figure 3
Figure 3
Forest plot for (A) injection-site adverse event, (B) MACEs, (C) all-cause mortality, (D) nasopharyngitis, and (E) new-onset or worsening T2DM between Inclisiran and control group [14,18,19,20,21,24].
Figure 3
Figure 3
Forest plot for (A) injection-site adverse event, (B) MACEs, (C) all-cause mortality, (D) nasopharyngitis, and (E) new-onset or worsening T2DM between Inclisiran and control group [14,18,19,20,21,24].
See this image and copyright information in PMC

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